Table 3.

Overview of potential CSF biomarkers shared between delirium and dementia

Biomarker	Cohort size				Findings	Ref.
	No delirium, no dementia	Dementia only	Delirium only	DSD
Systemic inflammation
IL-8	176	83	19	53	Among patients with HF without dementia, preoperative IL-8 levels were significantly higher in those who developed delirium than in those who did not; both cognitively healthy controls and patients with dementia had significantly lower levels of IL-8 than patients with HF	167
Total protein	0	20	20	0	Higher protein levels in participants with delirium than in participants with dementia	102
Neuroinflammation
(sTREM2)	44	10	15	50	In patients with HF, higher levels of CSF sTREM2 in delirium, but only in participants without pre-existing dementia	79
AD biomarkers
Aβ1–42	242	0	40	0	Higher CSF Aβ1–42 concentration predicted delirium	87
Aβ1–42, t-tau, Aβ1–42 to t-tau ratio, Aβ1–42 to p-tau ratio	49	10	16	54	Higher t-tau concentration and lower Aβ1–42, Aβ1–42 to t-tau ratio, and Aβ1–42 to p-tau ratio were associated with delirium, but only in individuals without dementia	88
Aβ1–40, Aβ1–42, t-tau, p-tau181	93	33	26	47	AD biomarkers were not associated with postoperative delirium	91
Aβ1–42 to t-tau ratio	122	Excluded	31	NA	Lower Aβ1–42 to t-tau ratio was associated with a greater likelihood of delirium	90
ATNa	53	0	6	0	Preclinical AD biomarkers (presence of amyloid) was associated with greater delirium severity	168
Neuronal injury
NfL	114	38	46	116	Higher NfL concentration was associated with delirium	103
S100B	83 (HF); 50 (ES)	49 (HF); 0 (ES)	52 (HF); 0 (ES)	39	Among patients with pathological levels of p-tau, an increase in S100B concentration was observed in patients with incident delirium compared with patients with no delirium	99
Lactate	0	20	20	0	Patients with delirium had higher lactate levels than patients with dementia	102
NSE	0	20	20	0	Patients with delirium had lower levels of NSE than patients with dementia	102
FABP3	171	10	16	55	No association with delirium; CSF FABP3 concentration was correlated with t-tau and p-tau levels	108
Other
Neurogranin	175	10	18	52	No association with delirium	110
Proteomics and metabolomics
Apolipoproteins and chromogranin and secretograninsb	8	17	17	0	Discovery proteomics study; identified upregulation of inflammatory proteins and downregulation of apolipoproteins and chromogranin and secretogranins in delirium compared with AD	112
Spermidine, glutamine, putrescinec	26	0	28	0	Targeted metabolomic study; elevated preoperative CSF spermidine, glutamine and putrescine predicted delirium; spermidine concentration was negatively correlated with Aβ1–42	113

Note that studies differ in methods and reporting standards, definitions and measures for delirium and dementia used, varying study populations, and presence of different comorbidities. Therefore, we report only positive or negative associations and not effect sizes, which were not directly comparable across studies. AD, Alzheimer disease; Aβ, amyloid-β; CSF, cerebrospinal fluid; DSD, delirium superimposed on dementia; ES, elective surgery; FABP3, fatty acid-binding protein 3; HF, hip fracture; NA, not available; NfL, neurofilament light; NSE, neuron-specific enolase; p-tau, phosphorylated tau; sTREM2, soluble fragment of triggering receptor expressed on myeloid cells; t-tau, total tau. ^aThe ATN biomarker framework is used to distinguish AD from non-AD causes of cognitive impairment with three types of biomarkers: β-amyloid deposition (A), pathological tau (phosphorylated tau, T) and neurodegeneration (total tau, N)⁶⁴. ^bSecretogranins associated with neurodegeneration. ^cPutrescine is elevated in AD and might be involved in amyloid plaque formation.